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Kasper D Tidemand, Hans E M Christensen, Niclas Hoeck, Pernille Harris, Jane Boesen, Günther H Peters
Tryptophan hydroxylase 2 (TPH2) catalyses the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression, obsessive compulsive disorder, and schizophrenia. Full-length TPH2 is poorly characterized due to low purification quantities caused by its inherent instability. Three truncated variants of human TPH2 (rch TPH2; regulatory and catalytic domain, NΔ47-rch TPH2; truncation of 47 residues in the N terminus of rch TPH2, and ch TPH2; catalytic domain) were expressed, purified, and examined for changes in transition temperature, inactivation rate, and oligomeric state...
October 2016: FEBS Open Bio
Zakariae Bram, Estelle Louiset, Bruno Ragazzon, Sylvie Renouf, Julien Wils, Céline Duparc, Isabelle Boutelet, Marthe Rizk-Rabin, Rossella Libé, Jacques Young, Dennis Carson, Marie-Christine Vantyghem, Eva Szarek, Antoine Martinez, Constantine A Stratakis, Jérôme Bertherat, Hervé Lefebvre
Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent hypercortisolism. The disease is primarily caused by germline mutations of the protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene, which induces constitutive activation of PKA in adrenocortical cells. Hypercortisolism is thought to result from PKA hyperactivity, but PPNAD tissues exhibit features of neuroendocrine differentiation, which may lead to stimulation of steroidogenesis by abnormally expressed neurotransmitters...
September 22, 2016: JCI Insight
Maeson S Latsko, T Lee Gilman, Lindsey M Matt, K Maria Nylocks, Karin G Coifman, Aaron M Jasnow
Poor inhibitory processing of negative emotional content is central to many psychiatric disorders, including depression and anxiety. Moreover, increasing evidence suggests that core aspects of emotion-inhibitory processing are largely inherited and as such may represent a key intermediate or risk-related phenotype for common affective diseases (e.g., unipolar depressive, anxiety disorders). The current study employed a candidate-gene approach in order to most effectively examine this complex behavioral phenotype...
2016: PloS One
Sergi Mas, Ana Blázquez, Natalia Rodríguez, Daniel Boloc, Amalia Lafuente, Joan A Arnaiz, Luisa Lázaro, Patricia Gassó
OBJECTIVE: Pharmacogenetic studies of fluoxetine in children and adolescents are scarce. After reporting the effect of genetic variants in genes related to the fluoxetine pharmacokinetics on clinical response in a pediatric population, we now evaluate the impact of genetic markers involved in its pharmacodynamics. PATIENTS AND METHODS: The assessment was performed in 83 patients after 12 weeks of fluoxetine treatment. The genetic association analysis included a total of 316 validated single nucleotide polymorphisms in 45 candidate genes involved in six different pathways...
November 2016: Pharmacogenetics and Genomics
Boris Mlinar, Alberto Montalbano, Lukasz Piszczek, Cornelius Gross, Renato Corradetti
Tonic spiking of serotonergic neurons establishes serotonin levels in the brain. Since the first observations, slow regular spiking has been considered as a defining feature of serotonergic neurons. Recent studies, however, have revealed the heterogeneity of serotonergic neurons at multiple levels, comprising their electrophysiological properties, suggesting the existence of functionally distinct cellular subpopulations. In order to examine in an unbiased manner whether serotonergic neurons of the dorsal raphe nucleus (DRN) are heterogeneous, we used a non-invasive loose-seal cell-attached method to record α1 adrenergic receptor-stimulated spiking of a large sample of neurons in brain slices obtained from transgenic mice lines that express fluorescent marker proteins under the control of serotonergic system-specific Tph2 and Pet-1 promoters...
2016: Frontiers in Cellular Neuroscience
Ali Karami, Dzolkhifli Omar, James M Lazorchak, Chee Kong Yap, Zailina Hashim, Simon C Courtenay
Influence of waterborne butachlor (BUC), a commonly used pesticide, on morphometric, biochemical, and molecular biomarkers was evaluated in juvenile, full sibling, diploid and triploid African catfish (Clarias gariepinus). Fish were exposed for 21 days to one of three concentrations of BUC [mean measured µg/L: 22, 44 or 60]. Unexposed (control) triploids were heavier and longer and had higher visceral-somatic index (VSI) than diploids. Also, they had lighter liver weight (HSI) and showed lower transcript levels of brain gonadotropin-releasing hormone (GnRH), aromatase (cyp191b) and fushi tarazu-factor (ftz-f1), and plasma testosterone levels than diploids...
August 11, 2016: Environmental Research
Zhi Xu, Gavin P Reynolds, Yonggui Yuan, Yanyan Shi, Mengjia Pu, Zhijun Zhang
BACKGROUND: Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms (SNPs) in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region SNPs identified significant associations of TPH2 and HTR1B SNPs with treatment response that showed interactions with childhood and recent life stress respectively (Xu et al, 2012)...
August 12, 2016: International Journal of Neuropsychopharmacology
C L Dent, T Humby, K Lewis, A Plagge, R Fischer-Colbrie, J F Wilkins, L S Wilkinson, A R Isles
Genomic imprinting is the process whereby germline epigenetic events lead to parent-of-origin specific monallelic expression of a number of key mammalian genes. The imprinted gene Nesp is expressed from the maternal allele only and encodes for Nesp55 protein. In the brain Nesp55 is found predominately in discrete areas of the hypothalamus and midbrain. Previously, we have shown that loss of Nesp55 gives rise to alterations in novelty-related behavior. Here we extend these findings and demonstrate, using the Nesp(m/+) mouse model, that loss of Nesp55 leads to impulsive choices as measured by a delayed-reinforcement task, whereby Nesp(m/+) mice were less willing to wait for a delayed, larger reward, preferring instead to choose an immediate, smaller reward...
August 10, 2016: Genes, Brain, and Behavior
Joanna Pawlak, Monika Dmitrzak-Weglarz, Monika Wilkosc, Aleksandra Szczepankiewicz, Anna Leszczynska-Rodziewicz, Dorota Zaremba, Pawel Kapelski, Aleksandra Rajewska-Rager, Joanna Hauser
INTRODUCTION: Studies have not given yet a clear answer what is the genetic background of suicidal predisposition. The associations between polymorphisms of the TPH1 and 5-HTTLPR genes and violent suicidal behavior was revealed with the least inconsistencies. METHOD: We selected 10 "strong candidate genes" and 35 SNPs, SLC6A4 and ACP1 for replication study. We searched associations between precisely described suicidal phenotype in 825 affective patients and polymorphisms of selected neurobiological pathways genes as well as their interactions that constitute suicidal risk...
July 19, 2016: Journal of Affective Disorders
Ali Karami, Nicholas Romano, Tamara Galloway, Hazilawati Hamzah
Despite the ubiquity of microplastics (MPs) in aquatic environments and their proven ability to carry a wide variety of chemicals, very little is known about the impacts of virgin or contaminant-loaded MPs on organisms. The primary aim of this study was to investigate the impacts of virgin or phenanthrene (Phe)-loaded low-density polyethylene (LDPE) fragments on a suite of biomarker responses in juvenile African catfish (Clarias gariepinus). Virgin LDPE (50 or 500µg/L) were preloaded with one of two nominal Phe concentrations (10 or 100µg/L) and were exposed to the fish for 96h...
July 21, 2016: Environmental Research
Andromeda Liñán-Rico, Fabio Turco, Fernando Ochoa-Cortes, Alan Harzman, Bradley J Needleman, Razvan Arsenescu, Mahmoud Abdel-Rasoul, Paolo Fadda, Iveta Grants, Emmett Whitaker, Rosario Cuomo, Fievos L Christofi
BACKGROUND: Clinical observations or animal studies implicate enteric glial cells in motility disorders, irritable bowel syndrome, inflammatory bowel disease, gastrointestinal (GI) infections, postoperative ileus, and slow transit constipation. Mechanisms underlying glial responses to inflammation in human GI tract are not understood. Our goal was to identify the "reactive human enteric glial cell (rhEGC) phenotype" induced by inflammation, and probe its functional relevance. METHODS: Human enteric glial cells in culture from 15 GI-surgical specimens were used to study gene expression, Ca, and purinergic signaling by Ca/fluo-4 imaging and mechanosensitivity...
August 2016: Inflammatory Bowel Diseases
Dragana Komnenov, Julia Z Solarewicz, Fareeza Afzal, Kwaku D Nantwi, Donald M Kuhn, Jason H Mateika
We examined the effect of repeated daily exposure to intermittent hypoxia (IH) on the recovery of respiratory and limb motor function in mice genetically depleted of central nervous system serotonin. Electroencephalography, diaphragm activity, ventilation, core body temperature, and limb mobility were measured in spontaneously breathing wild-type (Tph2(+/+)) and tryptophan hydroxylase 2 knockout (Tph2(-/-)) mice. Following a C2 hemisection, the mice were exposed daily to IH (i.e., twelve 4-min episodes of 10% oxygen interspersed with 4-min normoxic periods followed by a 90-min end-recovery period) or normoxia (i...
August 1, 2016: Journal of Applied Physiology
Takeshi Tanaka, Yasuko Hasegawa-Baba, Yousuke Watanabe, Sayaka Mizukami, Yumi Kangawa, Toshinori Yoshida, Makoto Shibutani
To elucidate the developmental exposure effects of ochratoxin A (OTA) on postnatal hippocampal neurogenesis, pregnant SD rats were provided a diet containing 0, 0.12, 0.6, or 3.0ppm OTA from gestation day 6 to day 21 on weaning after delivery. Offspring were maintained through postnatal day (PND) 77 without OTA exposure. At 3.0ppm, offspring of both sexes showed a transient body weight decrease after weaning. Changes in hippocampal neurogenesis-related parameters as measured in male PND 21 offspring were observed at 3...
June 23, 2016: Reproductive Toxicology
Honghai Zhang, Haiting Zhao, Xiaoxuan Yang, Qingsheng Xue, Joseph F Cotten, Hua-Jun Feng
OBJECTIVE: The DBA/1 mouse is a relevant animal model of sudden unexpected death in epilepsy (SUDEP), as it exhibits seizure-induced respiratory arrest (S-IRA) evoked by acoustic stimulation, followed by cardiac arrhythmia and death. Defects in serotonergic neurotransmission may contribute to S-IRA. The tryptophan hydroxylase-2 (TPH2) enzyme converts L-tryptophan to 5-hydroxytryptophan (5-HTP), a precursor for central nervous system (CNS) serotonin (5-HT) synthesis; and DBA/1 mice have a polymorphism that decreases TPH2 activity...
August 2016: Epilepsia
D V Bazovkina, A S Tsybko, E A Filimonova, T V Ilchibaeva, V S Naumenko
Tryptophan hydroxylase 2 (Tph-2) is the key enzyme in serotonin biosynthesis. Serotonin is one of the main neurotransmitters involved in the regulation of various physiological functions and behavior patterns. The influence of chronic ethanol consumption on the expression of the Bdnf, Bax, Bcl-xL, and CASP3 genes was studied in the brain structures of B6-1473C (C/C) and B6-1473G (G/G) mice that had been obtained on the base of the C57BL/6 strain. The strains differed in the genotype for the C1473G single nucleotide polymorphism in the Tph-2 gene and in Tph-2 enzyme activity...
March 2016: Molekuliarnaia Biologiia
Roberto Cilia, Roberta Benfante, Rosanna Asselta, Laura Marabini, Emanuele Cereda, Chiara Siri, Gianni Pezzoli, Stefano Goldwurm, Diego Fornasari
BACKGROUND: Impulse control disorders and compulsive medication intake may occur in a minority of patients with Parkinson's disease (PD). We hypothesize that genetic polymorphisms associated with addiction in the general population may increase the risk for addictive behaviors also in PD. METHODS: Sixteen polymorphisms in candidate genes belonging to five neurotransmitter systems (dopaminergic, catecholaminergic, serotonergic, glutamatergic, opioidergic) and the BDNF were screened in 154 PD patients with addictive behaviors and 288 PD control subjects...
August 2016: Parkinsonism & related Disorders
Amene Saghazadeh, Shadi A Esfahani, Nima Rezaei
INTRODUCTION: Heterogeneity of therapeutic response to brain stimulation techniques has inspired scientists to uncover the secrets to success or failure of these projects. Genetic polymorphisms are one of the major causes of this heterogeneity. AREAS COVERED: More than twenty genetic variants within more than ten genes (e.g. BDNF, COMT, DRD2, TRPV1, 5-HT1A, 5-HHT, P2RX7, VEGF, TPH1, TPH2, ACE, APOE, GNB3, NET, NMDA receptors, and RGS4) have been investigated, among which the BDNF gene and its polymorphism, Val66Met, is the best documented variant...
September 2016: Expert Review of Neurotherapeutics
David Coyle, Justin M Murphy, Brian Doyle, Anne Marie O'Donnell, John Gillick, Prem Puri
AIM: To determine if expression of colonic tryptophan hydroxylase-2 (TPH2), a surrogate marker of neuronal 5-hydroxytryptamine, is altered in Hirschsprung's-associated enterocolitis. METHODS: Entire resected colonic specimens were collected at the time of pull-through operation in children with Hirschsprung's disease (HSCR, n = 12). Five of these patients had a history of pre-operative Hirschsprung's-associated enterocolitis (HAEC). Controls were collected at colostomy closure in children with anorectal malformation (n = 10)...
May 21, 2016: World Journal of Gastroenterology: WJG
C Bonvicini, S V Faraone, C Scassellati
The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug...
July 2016: Molecular Psychiatry
Qiang Shen, Meijun Teo, Eyal Winter, Einav Hart, Soo H Chew, Richard P Ebstein
Although, lying (bear false witness) is explicitly prohibited in the Decalogue and a focus of interest in philosophy and theology, more recently the behavioral and neural mechanisms of deception are gaining increasing attention from diverse fields especially economics, psychology, and neuroscience. Despite the considerable role of heredity in explaining individual differences in deceptive behavior, few studies have investigated which specific genes contribute to the heterogeneity of lying behavior across individuals...
2016: Frontiers in Behavioral Neuroscience
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